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(Circulation Research. 2000;86:1187.)
© 2000 American Heart Association, Inc.

Editorials

Cytokine Actions of Angiotensin II

Junichi Sadoshima

From the Weis Center for Research, Pennsylvania State University College of Medicine, Danville, Pa.

Correspondence to Junichi Sadoshima, Weis Center for Research, Pennsylvania State University College of Medicine, Department of Molecular Cellular Physiology, 100 N Academy Ave, Danville, PA 17822. E-mail Jsadoshima@psghs.edu

Key Words: angiotensin II • nuclear factor-B • cytokine • AT₂

	Introduction

 
During the last few years, there has been an exponential rise in understanding functions and signal transduction mechanisms for angiotensin II (Ang II) type 2 receptors (AT₂s).^{1 2} These studies are particularly relevant in view of the pivotal role of upregulation of AT₂ in mediating tissue remodeling in many cardiovascular diseases, including vascular injury, atherosclerosis, cardiac hypertrophy, myocardial infarction, and congestive heart failure.¹ Furthermore, Ang II type 1 receptor (AT₁) antagonists, commonly used for treatment of hypertension and congestive heart failure, increase plasma levels of Ang II and upregulate AT₂ expression. Under these conditions, the increase in AT₂ is unopposed by AT₁.^{1 3} Thus, understanding the role of AT₂ in cardiovascular remodeling as well as the consequences of AT₂ stimulation or inhibition during medical therapy is clinically important. AT₂s only partially share the signaling mechanisms with AT₁s and, in fact, counteract the signaling mechanisms activated by AT₁s² (Figure). This negative nature of AT₂ signaling has made the elucidation of its function more difficult than that of AT₁. However, recent studies on the cardiovascular functions of AT₂ seem to have reached a consensus: AT₂s exert growth inhibitory effects either by suppressing cell proliferation and hypertrophy^{4 5} or by stimulating apoptosis.^{1 2 6} These actions alone may not explain the diverse cardiovascular phenomena attributed to AT₂, resulting in unanswered questions. Why are AT₂s abundant in growing fetal tissues? Why are AT₂s abundant in tissues undergoing remodeling? Recently, an elegant genetic study has provided an answer . . . [Full Text of this Article]

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